A search using the PICO criteria identified two systematic reviews with meta-analysis (Prakash, 2017; Reece-Smith, 2009), one RCT (Pere, 2016) and one RCT-based cost-effectiveness analysis (Nordin, 2017). The SR of Prakash (2017) included 11 studies representing 10 unique cohorts that compared local with spinal anaesthesia in 1377 unilateral inguinal hernia patients, 24 patients were women. The SR of Reece-Smith (2009) included 5 RCTs comparing local with general anaesthesia in 895 patients, 19 patients were women. One of the RCTs (O’Dwyer, 2003) included both unilateral (91.8%) and bilateral (8.2%) inguinal hernia patients. Another RCT included both primary (91.3%) and recurrent (8.7%) inguinal hernia patients. The review of Reece-Smith (2009) had some methodological shortcoming, for example the quality of individual studies was not assessed. The RCT of Pere (2016) randomized a total of 156 male patients into three groups: local, regional or general anaesthesia. This RCT had a high Risk of Bias (see quality of evidence table). Nordin (2007) used data of 616 patients collected during a RCT comparing local, regional and general anaesthesia to compare the costs of local, regional and general anaesthesia.

Results

Pain (crucial outcome)

Local versus regional anaesthesia

Five studies included in the systematic review of Prakash (2017) that compared local with regional anaesthesia reported on pain. Two studies graphically represented values and three studies (n=525 patients) reported on early post-operative pain (Figure 1). Mean pain score ranged from 1.8 to 24.2 in the local anaesthesia group, the mean pain score ranged from 3 to 31.3 in the regional group. The standardized mean difference was -0.63 (95% CI -0.81 to -0.46) in favour of local anaesthesia. In addition, the RCT of Pere 2016 comparing local with regional anaesthesia in 104 patients reported the median numerical rating scale (NRS) pain score at the first postoperative day and found no differences between groups (median was 4 in both groups). At the seventh postoperative day the median was 1 in both groups, with a range of 0-4 in patients with local anaesthesia and 0 to 7 in patients with regional anaesthesia.

The systematic review of Reece-Smith (2009) compared local with general anaesthesia but did not report on pain. Data extraction of individual studies showed different results. Three studies reported the mean VAS pain at different follow-up moments; two RCTs found a lower early postoperative mean pain in the group with local anaesthesia compared to the general anaesthesia group (time between leaving theatre and discharge from hospital: mean 1.8 (95% CI 1.6 to 2.0) versus 3.3 (95% CI 3.0 to 3.5), n=413; mean pain after 8 hours 2.12 (SD 1) versus 3.58 (SD 1.5), n=50; mean pain after 24 hours 1.2 (SD 1.1) versus 1.8 (SD 1.4), n=50). Another study graphically represented values of 50 patients and found that the local group had lower pain scores at the first hour after surgery. One study reported pain after 30 days, pain did not differ between groups (mean 1.1 (95% CI 0.9 to 1.3) versus 1.1 (95% CI 0.9 to 1.3), n=413). One RCT reported that patients with local anaesthesia had more pain (on movement) after 1 year compared to patients with general anaesthesia (mean VAS (0-100 scale) 8.8 (SD 14.7) versus 6.2 (SD 9.6), n=279). In addition, the RCT of Pere 2016 comparing local with regional anaesthesia in 104 patients reported the median numerical rating scale (NRS) pain score at the first postoperative day and found no differences between groups (median was 4 in both groups). At the seventh postoperative day the median was 1 with a range of 0-4 in both groups.

Quality of the evidence

Evidence originated from RCTs and the level of the quality of the evidence comparing local anaesthesia versus regional or general anaesthesia started therefore at ‘High’. However, the quality of the evidence was downgraded with three levels to ‘Very low’, for serious methodological limitations of the studies (Risk of Bias due to unclear allocation concealment, unclear blinding of outcome assessors and violation of the intent to treat analysis), for inconsistency (different types of surgical techniques, population (unilateral and bilateral, primary and recurrent hernias) and large confidence intervals in studies and indicating either an effect or no effect).

Recurrence (critical outcome)

Local versus regional anaesthesia

The review of Prakash (2017) identified three studies with a total of 562 patients that measured recurrence in the early post-operative period. Only one study reported the incidence of recurrence across both groups, but these rates were not significantly different (no values were reported). The short follow up time frame needs to be considered in the context of these results.

Local versus general anaesthesia

Two RCTs with 329 patients included in the review of Reece-Smith (2009) reported on recurrence. No recurrence was observed in both studies. The follow-up times of the RCTs were 1 year and 6 weeks.

Local versus regional and general anaesthesia

The RCT of Pere (2016) comparing local, regional and general anaesthesia (n=156 patients) with a follow-up of 3 months reported only one patient with recurrence (not reported in which group) in whom about 1.5 months after the primary repair of a large medial hernia a new smaller medial hernia had developed in the same region, and it was successfully repaired laparoscopically.

Quality of the evidence

Evidence originated from RCTs and the level of the quality of the evidence comparing local anaesthesia versus regional or general anaesthesia started therefore at ‘High’. However, the quality of the evidence was downgraded with three levels to ‘Very low’, for serious methodological limitations of the studies (Risk of Bias due to unclear allocation concealment, unclear blinding of outcome assessors and violation of the intent to treat analysis), for inconsistency (different types of surgical techniques, population (unilateral and bilateral, primary and recurrent hernias) and for imprecision (very low number of events).

Urinary retention (important outcome)

Local versus regional anaesthesia

Nine studies included in the systematic review of Prakash (2017) comparing local with regional anaesthesia and the RCT of Pere 2016 reported on urinary retention (Figure 2). Urinary retention was reported in 0.1% (1/695) of the patients in the local anaesthesia group versus 20.7% (142/687) of those with regional anaesthesia (RR 0.06, 95% CI 0.02 to 0.15).

Figure 2. Local versus spinal anaesthesia. Outcome: urinary retention

Local versus general anaesthesia

Four studies included in the systematic review of Reece-Smith (2009) comparing local with general anaesthesia and the RCT of Pere (2016) reported on urinary retention (Figure 3). Urinary retention was reported in 2.7% (8/293) of the patients in the local anaesthesia group versus 4.5% (13/290) of those with regional anaesthesia (RR 0.65, 95% CI 0.29 to 1.45).

Evidence originated from RCTs and the level of the quality of the evidence comparing local anaesthesia versus regional or general anaesthesia started therefore at ‘High’. However, the quality of the evidence was downgraded with three levels to ‘Very low’, for serious methodological limitations of the studies (Risk of Bias due to unclear allocation concealment, unclear blinding of outcome assessors and violation of the intent to treat analysis), for inconsistency (different types of surgical techniques, population (unilateral and bilateral, primary and recurrent hernias) and for imprecision (very low number of events).

Length of stay (important outcome)

Local versus regional anaesthesia

The outcome measure length of stay was not reported in the systematic review of Prakash (2017). The RCT of Perre (2016) reported the median time from start of anaesthesia until readiness for discharge in minutes. Patients in the local anaesthesia group were discharged after a median of 93 minutes (Inter Quartile Range (IQR) 46) and patients in the regional anaesthesia group were discharged after a median of 190 minutes (IQR 54).

Local versus general anaesthesia

Two studies in the systematic review of Reece-Smith (2009) reported the postoperative stay and both studies found that patients in the local anaesthesia group had a shorter postoperative hospital stay compared with the general anaesthesia group (mean 3.1 (95% CI 2.8-3.4) versus 6.2 (95% CI 5.5-6.8) hours, n=413 and median 22 (range 23) versus 28 (range 17) hours, n=50). Another study reported the mean length of stay in days and found a mean of 3.1 (SD 0.8) days in the local anaesthesia group versus 3.2 (1.2) days in the general anaesthesia group in a total of 279 patients. One study reported discharge at 24 hours, 46 (87%) of the 53 patients in the local anaesthesia group were discharged at 24 hours versus 47 (94%) of the 50 patients in the general anaesthesia group. The RCT of Perre (2016) reported the median time from start of anaesthesia until readiness for discharge in minutes. Patients in the local anaesthesia group were discharged after a median of 93 minutes (Inter Quartile Range (IQR) 46) and patients in the general anaesthesia group were discharged after a median of 142 minutes (IQR 35).

Quality of the evidence

Evidence originated from RCTs and the level of the quality of the evidence comparing local anaesthesia versus regional or general anaesthesia started therefore at ‘High’. However, the quality of the evidence was downgraded with three levels to ‘Very low’, for serious methodological limitations of the studies (Risk of Bias due to unclear allocation concealment, unclear blinding of outcome assessors and violation of the intent to treat analysis), for inconsistency (different types of surgical techniques, population (unilateral and bilateral, primary and recurrent hernias) and studies and indicating either an effect or no effect) and for imprecision (sample size <2000).

Patients satisfaction (important outcome)

Local versus regional anaesthesia

Three studies included in the systematic review of Prakash (2017) comparing local with regional anaesthesia and the RCT of Pere 2016 reported on patients satisfaction (Figure 4). Patients satisfaction was reported in 86.6% (219/253) of the patients in the local anaesthesia group versus 68.5% (172/251) of those with regional anaesthesia (RR 1.21, 95% CI 0.97 to 1.51).

Two studies in the systematic review of Reece-Smith (2009) reported patients satisfaction. One study reported that 96% (24/25) of the patients in the local anaesthesia group versus 71% (17/24) of the patients in the general anaesthesia group were satisfied. Another study reported the mean satisfaction score on a 1 to 10 scale. Patients in the local anaesthesia group had a mean satisfaction score of 8.1 (SD 1.4) compared to patients with a mean satisfaction score of 7.7 (SD 1.5) in the general anaesthesia group. The RCT of Pere (2016) reported that 96% (24/25) of the patients in the local anaesthesia group versus 100% (25/25) of the patients in the general anaesthesia group were satisfied.

Quality of the evidence

Evidence originated from RCTs and the level of the quality of the evidence comparing local anaesthesia versus regional or general anaesthesia started therefore at ‘High’. However, the quality of the evidence was downgraded with three levels to ‘Very low’, for serious methodological limitations of the studies (Risk of Bias due to unclear allocation concealment, unclear blinding of outcome assessors and violation of the intent to treat analysis), for inconsistency (different types of surgical techniques, population (unilateral and bilateral, primary and recurrent hernias) and studies and indicating either an effect or no effect) and for imprecision (sample size <2000).

Cost-effectiveness (important outcome)

One study (Nordin, 2007) assessed the costs of local, regional and general anaesthesia in non-teaching hospitals in Sweden that did not specialize in hernia surgery. Compared with general and regional anaesthesia, local anaesthesia is less expensive when hospital and total healthcare costs are considered. Compared with total healthcare costs for local anaesthesia, regional and general anaesthesia were €333 (15.7 per cent) and €316 (15.0 per cent), respectively, more expensive. In terms of total relevant costs to society, including loss of production, there was no significant difference in costs between the three groups.

Quality of the evidence

Evidence originated from RCTs and the level of the quality of the evidence comparing local anaesthesia versus regional or general anaesthesia started therefore at ‘High’. However, the quality of the evidence was downgraded with three levels to ‘Very low’, for methodological limitations of the study (it was described as a cost-effectiveness study, but only costs were provided and no cost-effectiveness analysis was performed), indirectness (costs were calculated for Sweden with a different health care system) and for imprecision (only one study with a sample size <2000).

The clinical question comparing general or regional anaesthesia was answered based on the International Guidelines (HerniaSurge Group, 2018) and no systematic literature search was done for this question. In order to answer the clinical question Does local anaesthesia influence outcomes after open inguinal hernia repair compared to general or regional anaesthesia? A systematic literature search was done:

The working group decided that pain and recurrence were crucial outcome measures for decision-making and urinary retention, length of stay, patients satisfaction and cost-effectiveness important outcome measures for decision-making. The working group did not define the mentioned outcome measures beforehand, however, they used the definitions described in the studies.

Searching and selecting (Methods)

The information specialist from the Cochrane Centre in the Netherlands searched Medline and Embase on April 11th 2017 and the Cochrane Register on April 12th 2017 for systematic reviews (SRs) and randomized controlled trials (RCTs) about inguinal hernias, without restrictions on publication date. All duplicates (including duplicates from the former search on the 30th of June 2015) were removed. The search details can be found in the tab Acknowledgement.

Literature experts excluded studies that were clearly not relevant for answering clinical questions about inguinal hernias. Therefore, 66 SRs and 241 RCTs remained to be judged by the working group.

The working group selected 49 studies based on title-abstract, that could possibly answer the research question. The world guideline yielded four relevant studies, therefore, 53 studies were read full text. After reading full text, 49 studies were excluded (see exclusion table in the tab Acknowledgement); finally, 4 studies were included for analysis: three studies from the search of the Cochrane Centre and one study from the world guideline (Nordin, 2007; Pere, 2016; Prakash, 2017; Reece-Smith, 2009).

Data extraction and analysis

The most important study characteristics and results were extracted from the SRs or original studies (in case of missing information in the review). The most important study characteristics and results are shown in the evidence tables. The judgement of the individual study quality (Risk of Bias) is shown in the Risk of Bias tables.

Relevant pooled and/or standardised effect measures were, if useful, calculated using Review Manager 5.3 (Cochrane Collaboration, Oxford, United Kingdom). If pooling results was not possible, the outcomes and results of the original study were used as reported by the authors.

De working group did not define clinical (patient) relevant differences for the outcome measures. Therefore, we used the following boundaries for clinical relevance, if applicable: for continue outcome measures: RR<0.75 or >1.25 (GRADE recommendation) or Standardized mean difference (SMD=0.2 (little); SMD 0.5 (reasonable); SMD=0.8 (large). These boundaries were compared with the results of our analysis. The interpretation of dichotomous outcome measures is strongly related to context; therefore, no clinical relevant boundaries were set beforehand. For dichotomous outcome measures, the absolute effect was calculated (Number Needed to Treat (NNT) or Number Needed to Harm (NNH)).

In this review, we identified three papers (B, F, J) that measured recurrence in the early post-operative period. Only one study reported incidence of recurrence across both groups, but these rates were not significantly different. However, the follow up time frame needs to be considered in the context of these results (no values were reported).

Facultative:

Author’s conclusion

This systematic review evaluated the totality of evidence from ten unique RCTs on the effectiveness of local anaesthesia when compared to spinal anaesthesia in adult patients

undergoing open inguinal hernia repair for a primary inguinal hernia. A range of self-report and objective

clinical measures were included in the studies. Findings from the pooled analysis demonstrate that there are no significant differences between the groups with regard

to operative time, wound haematoma, wound infection

and recurrence. However, patients who underwent a local anaesthetic repair presented with significantly less rates of urinary retention, reduced pain scores and lower

anaesthetic failures than those who underwent a spinal

anaesthetic repair. Patient satisfaction with the anaesthesia was also significantly higher in the local anaesthetic group.

Level of evidence: GRADE in SR not reported

Reece-Smith 2009

PS., study characteristics and results are extracted from the SR (unless stated otherwise)

SR and meta-analysis of RCTs

Literature search up to May 2008

A: O’Dwyer 2003

B: Teasdale 1982

C: Nordin 2003

D: Özgün 2002

E: Gönüllü 2002

Study design: RCT

Setting and Country: United Kingdom

Source of funding:

Not reported.

Inclusion criteria SR:

Randomised controlled trials comparing

outcomes from local and general anaesthetic

used in inguinal hernia repair. Fifty different outcome measures were recorded in

five of the trials identified, but only those assessed in at least three studies were considered for meta-analysis.

reported by the individual studies. Local anaesthetic reduces nausea and accelerates return to normal activities following open inguinal hernia repair. The benefit of LA is sufficiently small that its use should be dictated by patient and clinician preference.

Research question: Does local anesthesia influence outcomes after open inguinal hernia repair compared to general or regional anesthesia?

Study reference

Study characteristics

Patient characteristics 2

Intervention (I)

Comparison / control (C) 3

Follow-up

Outcome measures and effect size 4

Comments

Pere 2016

Type of study: RCT (3 arms)

Setting: University hospital day-surgery center

Country:

Finland

Source of funding:

Funded by study grants from Finska Läkaresällskapet, Finland

Inclusion criteria: Male patients, scheduled for open unilateral inguinal herniorrhaphy in the day surgery center for eligibility to participate in the study.

Exclusion criteria:

The most common

refusal reason (76%) was the patient's own wish for a certain

anesthetic technique, while some patients refused to have

one of the presented three techniques. Other exclusion criteria were BMI> 40 kg/m2, BMI<15 kg/m2, scrotal

hernias, severe renal, cardiac or hepatic insufficiency,

coagulation disorder, local anesthetic allergy, lack of co-operation due to cognitive impairment or inadequate ability to communicate because of linguistic problems.

N total at baseline:

Intervention (LAI): 52

Control (SPIN): 52

Control (TIVA): 52

Important prognostic factors2:

Age, mean (SD):

I (LAI): 51 (16)

C (SPIN): 51 (15)

C (TIVA): 54 (15)

Weight , mean (SD):

I (LAI): 78 (8)

C (SPIN): 81 (9)

C (TIVA): 79 (10)

ASA 1/2/3 (n)

I (LAI): 31/ 20/ 1

C (SPIN): 25/ 19/ 5

C (TIVA): 23/ 25/ 3

International Prostatic Symptoms Score, mean (SD):

I (LAI): 5.9 (7.2)

C (SPIN): 5.9 (5.9)

C (TIVA): 7.7 (7.3)

Groups comparable at baseline? Yes

Describe intervention (treatment/procedure/test):

Local anesthetic infiltration (LAI)

First 15–18 mL of lidocaine 10 mg/mL with epinephrine

5 μg/mL was infiltrated in the skin and the subcutaneous layer of the incisional area. Then 15–18 mL of ropivacaine 7.5 mg/mL was injected into the deeper layers. The rest (left in both 20-mL syringes) of the local anesthetics was infiltrated under the fascia, around the funiculus (spermatic cord) and into the tissues at the base of

the hernia sac. Intraoperatively, supplemental lidocaine was

infiltrated (maximum 200 mg), as required to anesthetize the deeper layers, and fentanyl (25 or 50 μg IV once or twice) was given as needed if pain was felt by the patient. If

adequate analgesia could not be achieved with the

supplementation of local infiltration anesthesia, total

intravenous anesthesia with propofol and laryngeal mask

airway (LMA) was induced.

Describe control (treatment/procedure/test):

Control 1: Spinal anesthesia (SPIN)

With the patient in the lateral horizontal position and the side of operation dependent a 27 G needle with pencil-point tip was inserted in the midline through the L3–4 intervertebral space. The drug mixture was hyperbaric bupivacaine 6 mg (Bicain Pond Spinal®, Orion Pharma, Espoo, Finland) and 10 μg of fentanyl. After the injection the operating table was tilted head-down 10° and the lateral position maintained for 5 minutes. Then the patient was placed supine on the table, which was returned to its neutral horizontal position, except when the sensory block had not yet spread to the T10

dermatome level (tested by pin-prick). If analgesia was inadequate during surgery, fentanyl 25 or 50 μg IV was administered. If surgical pain persisted after two doses of fentanyl, anesthesia was supplemented with

lidocaine infiltration or total intravenous anesthesia (propofol, remifentanil, LMA and mechanical ventilation). At the end of the operation, the surgeon infiltrated the tissue layers between the fascia and the skin with 20 mL of ropivacaine 7.5 mg/mL.

Control 2: Total intravenous anesthesia (TIVA)

Fentanyl 1.5 μg/kg IV was administered followed by

propofol 2–2.5 mg/kg, and an LMA was placed, following which the patient was mechanically ventilated. For maintenance propofol and remifentanil were intravenously infused.

No anticholinergics or neuromuscular blocking agents were used. Anesthesia depth was maintained at 40–60 on the

Entropy™ monitor (GE Healthcare, Helsinki, Finland), and adjusted as needed by changing the infusion rate of propofol. Similarly to the SPIN group, at the end of surgery the wound was infiltrated with 20 mL of ropivacaine 7.5 mg/mL.

Length of follow-up: 3 months

Loss-to-follow-up:

Intervention (LAI):

1 (2%) at 3 months interview

Control (SPIN):

0

Control (TIVA):

1 (2%) at 3 months interview

Incomplete outcome data:

Intervention (LAI):

1 (2%)

Reason: patient was not reached by telephone at 3 months

Control (SPIN):

3 (6%)

Reason: patients were excluded because they did not receive allocated intervention after randomization because surgery was cancelled.

Control (TIVA):

2 (4%)

Reasons: 1 patient was not reached by telephone at 3 months, 1 patient was excluded because the anaesthetic plan was changed after randomization.

Defined as time from start of anesthesia until readiness for discharge (min), median (IQR)

I (LAI): 93 (46)

C (SPIN): 190 (54)

C (TIVA): 142 (35)

P<0.001

Patients satisfaction

I (LAI): 3 patients were dissatisfied with their anesthetic because of pain they had felt intraoperatively

C (SPIN): Four patients reported dissatisfaction with their anesthetic, two because of multiple attempts needed to

perform the intrathecal puncture and two (one of them very dissatisfied) because of an inadequate block.

C (TIVA): 0

Cost-effectiveness

Not reported

Recurrence

Recurrence was noted in only

one patient in whom about 1.5 months after the primary

repair of a large medial hernia a new smaller medial hernia

had developed in the same region, and it was successfully

repaired laparoscopically (not reported in which group).

Author’s conclusion:

With regard to the day-surgery setting, LAI anesthesia

was favorable since the patients could often ambulate

immediately after surgery, thus bypassing PACU1, and the

discharge criteria were met significantly earlier than in

patients having had general or spinal anesthesia. There was

no statistically significant difference in the high degree of patient satisfaction with their anesthesia in all three groups. Contrary to the situation in the LAI and SPIN groups with some anesthetic failures, and the frequent need for analgesia supplementation in the LAI group, in the TIVA group the anesthetics were always successful but needed frequently interventional attendance by the anesthesiologist. The lack of postoperative urinary retention in all our patients may be due to the small infused fluid volumes together with the routine bladder scan before and after surgery. Postoperative discomfort or pain in the groin in some patients was not associated with any particular anesthesia technique.

Nordin 2007

Type of study: Cost–effectiveness analysis using data from an RCT

Setting:

General surgical practice

Country:

Sweden

Source of funding:

Financial support for the Swedish Hernia Register is

provided by the National Board of Health and Welfare, and the Federation of County Councils, Sweden. The

study was supported by the Health Research Council of the south-east region of Sweden

An assessment of publication bias should include a combination of graphical aids (For example funnel plot, other available tests) and/or statistical tests (For example Egger regression test, Hedges-Olken). Note: If no test values or funnel plot included, score “no”. Score “yes” if mentions that publication bias could not be assessed because there were fewer than 10 included studies.

Sources of support (including commercial co-authorship) should be reported in both the systematic review and the included studies. Note: To get a “yes,” source of funding or support must be indicated for the systematic review AND for each of the included studies.

Research question: Does local anesthesia influence outcomes after open inguinal hernia repair compared to general or regional anesthesia?

Study reference

(first author, publication year)

Describe method of randomisation1

Bias due to inadequate concealment of allocation?2

(unlikely/likely/unclear)

Bias due to inadequate blinding of participants to treatment allocation?3

(unlikely/likely/unclear)

Bias due to inadequate blinding of care providers to treatment allocation?3

(unlikely/likely/unclear)

Bias due to inadequate blinding of outcome assessors to treatment allocation?3

(unlikely/likely/unclear)

Bias due to selective outcome reporting on basis of the results?4

(unlikely/likely/unclear)

Bias due to loss to follow-up?5

(unlikely/likely/unclear)

Bias due to violation of

intention to treat analysis?6

(unlikely/likely/unclear)

Pere 2016

Patients were randomized using the sealed envelope method.

Unclear

Likely

Likely

Likely

Unlikely

Unlikely

Likely

Randomisation: generation of allocation sequences have to be unpredictable, for example computer generated random-numbers or drawing lots or envelopes. Examples of inadequate procedures are generation of allocation sequences by alternation, according to case record number, date of birth or date of admission.

Allocation concealment: refers to the protection (blinding) of the randomisation process. Concealment of allocation sequences is adequate if patients and enrolling investigators cannot foresee assignment, for example central randomisation (performed at a site remote from trial location) or sequentially numbered, sealed, opaque envelopes. Inadequate procedures are all procedures based on inadequate randomisation procedures or open allocation schedules.

Blinding: neither the patient nor the care provider (attending physician) knows which patient is getting the special treatment. Blinding is sometimes impossible, for example when comparing surgical with non-surgical treatments. The outcome assessor records the study results. Blinding of those assessing outcomes prevents that the knowledge of patient assignement influences the proces of outcome assessment (detection or information bias). If a study has hard (objective) outcome measures, like death, blinding of outcome assessment is not necessary. If a study has “soft” (subjective) outcome measures, like the assessment of an X-ray, blinding of outcome assessment is necessary.

Results of all predefined outcome measures should be reported; if the protocol is available, then outcomes in the protocol and published report can be compared; if not, then outcomes listed in the methods section of an article can be compared with those whose results are reported.

If the percentage of patients lost to follow-up is large, or differs between treatment groups, or the reasons for loss to follow-up differ between treatment groups, bias is likely. If the number of patients lost to follow-up, or the reasons why, are not reported, the Risk of Bias is unclear.

Participants included in the analysis are exactly those who were randomized into the trial. If the numbers randomized into each intervention group are not clearly reported, the Risk of Bias is unclear; an ITT analysis implies that (a) participants are kept in the intervention groups to which they were randomized, regardless of the intervention they actually received, (b) outcome data are measured on all participants, and (c) all randomized participants are included in the analysis.

Risk of Bias table for cost-effectiveness study

CHEC-list

YES

NO

1.

Is the study population clearly described?

X

2.

Are competing alternatives clearly described?

X

3.

Is a well-defined research question posed in answerable form?

X

4.

Is the economic study design appropriate to the stated objective?

X

5.

Is the chosen time horizon appropriate in order to include relevant costs and consequences?

X

6.

Is the actual perspective chosen appropriate?

X

7.

Are all important and relevant costs for each alternative identified?

X

8.

Are all costs measured appropriately in physical units?

X

9.

Are costs valued appropriately?

X

10.

Are all important and relevant outcomes for each alternative identified?

X

11.

Are all outcomes measured appropriately?

X

12.

Are outcomes valued appropriately?

X

13.

Is an incremental analysis of costs and outcomes of alternatives performed?

X

14.

Are all future costs and outcomes discounted appropriately?

X

15.

Are all important variables, whose values are uncertain, appropriately subjected to sensitivity analysis?

X

16.

Do the conclusions follow from the data reported?

X

17.

Does the study discuss the generalizability of the results to other settings and patient/client groups?

X

18.

Does the article indicate that there is no potential conflict of interest of study researcher(s) and funder(s)?